At present, the implantable medical devices are usually made from metals and their alloys, ceramics, polymers and the related composite materials, wherein the metal materials are particularly popular because of their superior mechanical properties, such as high strength, and high toughness.
Iron as an important element in the human body, is involved in many biochemical processes, such as oxygen carrying. Easily corrosive pure iron stents each having a shape similar to that of a clinically used metal stent, made by Peuster M et al. through a laser engraving method, were respectively implanted to the descending aortas of 16 New Zealand rabbits. The animal experimental results showed that there was no thrombosis within 6 to 18 months, and also no adverse events occurred. The pathological examination confirmed that there were no inflammation in local blood vessel walls and no obvious proliferation on smooth muscle cells, preliminarily indicating that the degradable iron stent has good application prospects. But the study also found that the corrosion rate of pure iron was relatively slow in vivo environment, thus the corrosion rate needs to be accelerated. Various techniques for improving the corrosion rate of iron have been continuously developed, including alloying and metallurgical vessel changing methods.
The degradable polyester mainly comprises polylactic acid (PLA), polyglycolic acid (PGA) and poly (lactic acid-co-glycolic acid) (PLGA), polycaprolactone (PCL), etc. These polymers have been widely applied to biomedical engineering materials, such as surgical sutures, bone fixation, vascular repair materials and drug controlled release systems, etc. because of their excellent biocompatibility and bioabsorbability. Among them, the Biomatrix drug-eluting stent made by the Biosensor Company takes 316L stainless steel as a substrate, and PLA as a drug carrier for carrying a Biolimus drug, and the polymer coating can completely degrade within 6 to 9 months; a Synergy drug-eluting stent made by Boston Scientific Corporation takes a Pt—Cr alloy as a substrate, and PLGA as a drug carrier for carrying an Everolimus drug, and the polymer coating can completely degrade within 4 months. At present, there are many companies using poly (L-lactic acid) (PLLA) with a slow rate of degradation to make a completely degradable vascular stent with an absorption period of 2 to 3 years. It can be seen from the above examples that different degradable polyesters have different degradation and absorption periods.
It's been reported that if the surface of the iron-based alloy (including pure iron and medical iron-based alloys) stent was coated with a degradable polyester coating, the degradable polyester coating would produce a product with a carboxyl group in the degradation process in the human body, so that the pH value of the local microenvironment around the implantation position dropped to form a local subacid environment, the overpotential of hydrogen evolution reaction on the surface of the iron-based alloy substrate was reduced, and the hydrogen evolution corrosion was produced in the iron-based alloy substrate, thus producing an iron salt as a degradation product. It was reported that the degradable polyester could be used as the coating of the iron-based alloy substrate to speed up the hydrogen evolution corrosion rate of the iron-based alloy substrate, and reduce the toxic reaction of the stent at the initial stage of degradation, thus being favorable for rapid endothelialization of endothelial cells on the surface of the stent. However, the local subacid environment and the hydrogen evolution have not been confirmed in the industry, and the matching between the degradable polymer degradation and the iron substrate corrosion was not involved in the report.
Human vessels belong to an aqueous system, an oxygen-consuming corrosion can be produced in the iron-based alloy in the vessels to generate Fe (OH)2, and Fe (OH)2 which is quickly oxidized to generate a Fe (OH)3 precipitate (as shown in Formulas 1.1 and 1.2) at the same time. And the metabolism of Fe (OH)2 and Fe (OH)3 as water insolubles in the human body are mainly realized by cell phagocytosis, trace Fe ion ionization and other ways, and metabolism and absorption are slowly carried out. At the same time, corrosion products are wrapped around an iron implant to hinder the diffusion of O2 to Fe and reduce the corrosion rate, thus being unfavorable for further metabolism and absorption of iron.2Fe+2H2O+O2=2Fe(OH)2↓  (Formula 1.1)4Fe(OH)2+O2+2H2O=4Fe(OH)3↓  (Formula 1.2)
Our early experiments showed that the corrosion rate was greatly reduced after introducing nitrogen and removing oxygen in the corrosion environment. Therefore, we believe that the iron corrosion in the human body is not the hydrogen evolution corrosion as reported, in contrast, the oxygen-consuming corrosion is the most likely or leading reaction.
Our early experiments and theoretical studies also showed that the degradable polyester produced a product with the carboxyl group in the process of degradation, the product with the carboxyl group was coordinated with Fe2+ to form a coordination compound, such as ferrous lactate, ferrous acetate and ferrous glycinate (as shown in Formulas 2.1 and 2.2), and such corrosion product was a water soluble iron salt and could be quickly absorbed by the human body. At the same time, the water soluble iron salt could be diffused to other positions of the human body in body fluids, and there was no solid product produced around the iron implant to hinder the direct contact between Fe and O2 so as to accelerate the corrosion of Fe.R1COOR2+H2O=R1COOH+R2OH  (Formula 2.1)Fe(OH)2+2RCOO−═(RCOO)2Fe+2OH−  (Formula 2.2)
The degradable polyester may accelerate the corrosion of the iron-based alloy, and the concentration of iron ions is increased by providing local lactate ions; however, whether the degradation rate of the degradable polyester matches the corrosion rate of the iron-based alloy or not affects the form of the final corrosion product and the iron corrosion period length. Specifically, when the corrosion rate is too fast, the structural integrity and mechanical properties of the implanted iron-based alloy stent at early stage (such as 3 months) will be affected; if the release of iron ions exceeds the absorption power of blood vessels, iron formed by corrosion will be deposited as solid iron rust again in peripheral blood vessels at a certain distance from the implantation position, and remains in the human body for a long time. When the corrosion rate is not enough, the enhancement of the degradable polyester working on the corrosion rate of iron is limited, resulting in a relatively long degradation period of the iron-based alloy stent, for example, for a coronary stent, the stent cannot completely degrade and be absorbed within 1 to 3 years after implantation; for a peripheral vascular stent, the stent cannot completely degrade and be absorbed within 2 to 4 years after implantation yet, which is difficult to highlight the characteristics of degradation and absorption of the iron-based alloy stent. Moreover, whether the corrosion period of the iron-based alloy substrate is matched with the degradation period of the degradable polyester or not also strongly affects the overall degradation period of the iron stent. For example, if the degradable polyester only exists at early stage of corrosion of the iron-based alloy and accelerates the corrosion of the iron-based alloy, after the completion of degradation of the degradable polyester at late stage, the iron-based alloy has not completely corroded, the degradation rate of the remaining iron-based alloy will be relatively slow and the solid iron rust is formed, resulting in the relatively long overall degradation period of the iron-based alloy stent which still cannot meet the clinical time requirement of degradation and absorption of the degradable stent.
Therefore, it is necessary to provide a degradable polyester which can be matched with the iron-based alloy substrate to obtain an absorbable iron-based alloy stent capable of rapidly and controllably degrading within a predetermined period of time.